Phosphonic acids are a potent, yet underexploited, group of compounds with great promise in the treatment of human disease. Numerous structurally distinct phosphonates are produced in nature and many have useful bioactive properties. Importantly, the biological targets of phosphonic acids vary substantially, allowing them to be used for treating a variety of health conditions. The potent bioactivity of phosphonates also allows their use as fungicides, herbicides and pesticides. In our Initial funding period we showed that phosphonate biosynthesis is surprisingly common in nature and that a wealth of uncharacterized natural products await characterization. In this sub-project we propose a series of molecular, genetic and biochemical experiments aimed at exploiting and expanding these discoveries.